The aim is to improve the treatment of small cell carcinoma of the lung by learning more about the pathobiology of this tumor. All proposed studies involve the measurement of vasopressin and of its associated protein, vasopressin-neurophysin (VP-NP), by means of radioimmunoassay (RIA). Other methods include polyacrylamide gel electrophoresis, chromatography and amino acid analysis. The rate of production of VP and VP-NP will be measured in cultures of small cell carcinoma which already exist at Dartmouth Medical School. Knowing the rate of production of these substances, and their volume of distribution and half-life, the size of the tumor in vivo can be estimated by measuring the plasma concentration and urinary excretion of VP and VP-NP in patients. Our calculations suggest that we can probably monitor residual tumor volume that is about 100-fold smaller than what can be observed by current diagnostic means. By distinguishing autonomous production of VP and VP-NP by tumor, from normal hypothalamic production, it may be possible to push therapy to the point where no residual tumor remains. The proposed approach has precedents in analogous use of ectopic production of myeloma protein, human chorionic gonadotropin, and calcitonin. We propose to go further, however, by looking for other tumor markers, which might be identified and characterized by their physical and chemical properties. Such extension to other hormones and their metabolic products might broaden the applicability of the proposed approach to most or all small cell carcinomas. BIBLIOGRAPHIC REFERENCES: North, W.G., and Valtin, H. The purification of rat neurophysins by a method of polyacrylamide gel electrophoesis. Analyt. Biochem. 78:436, 1977. North, W.G., Valtin, H., Morris J.F., and LaRochelle, F.T., Jr. Evidence for metabolic conversions of rat neurophysins within neurosecretory granules of the hypothalamo-neurohypophysial system. Endocrinology, July, 1977, in press.